Amnir Pharmaceuticals recently announced that the FDA has accepted review of its New Drug Application (NDA) for IPX203 for the treatment of Parkinson’s disease (PD). IPX203 has been assigned a Prescription Drug Fee Act (PDUFA) effective date of June 30, 2023.
PD is the fastest growing neurological disorder in the world, with approximately 1 million people diagnosed in the United States. Carbidopa/levodopa (CD/LD) has been the main treatment for PD since the 1970s. Pivotal Phase 3 RISE-PD clinical trial data show that IPX203, a novel oral formulation of carbidopa/levodopa (CD/LD) sustained release capsules, not only provided excellent “good on” times, but also demonstrated “off” It has been shown to reduce the time significantly. Even with less frequent dosing, compared to immediate-release CD/LD, this means a longer period of symptom control with the benefit of less frequent dosing, allowing people with PD to better understand their symptoms and mobility. It may allow you to live with less worry.
DocWire News Spoken Richard D’Souza, PhD, SVP, Amneal’s Specialty R&D We shared details of Amneal’s recent NDA filing for IPX-203 and the supporting data used in the filing.
DocWire News: Could you tell us about your own background?
Dr. Richard D’Souza: yes. My name is Richard D’Souza. He holds a PhD in Clinical Pharmacology. I have been in the industry for over 35 years, working for Pfizer, Johnson & Johnson, Bausch & Lomb, and Amneal for about 4 years.
Parkinson’s disease (PD) cases are increasing worldwide. why is that?
It is mostly related to demographics. This is a disease that is seen more often as we get older, and is therefore seen more often.
Traditionally, what are the challenges of PD treatment?
Parkinson’s disease is a disease in which certain parts of the brain stop working. In other words, in the part of the brain that makes dopamine, the neurons that produce dopamine are not working, so dopamine is deficient. The intuitive answer is, can giving dopamine help the disease? Because dopamine does not cross the blood-brain barrier, there is no way to administer dopamine directly to the brain. So about 50 years ago, levodopa was invented and given together with carbidopa to have fewer side effects and last a little longer. The drug was called Sinemet. Immediate release carbidopa Levodopa, I call it CD-LD.
It works very well in the early stages, but as the disease progresses, there are peaks and troughs in blood levels of levodopa, and it actually stops working after a while. Many drugs have side effects. When it’s in the trough, you get two little pills, so you’re affected by Parkinson’s disease, including tremors and many things.
Talk to us about IPX203, a new treatment for PD. how does that work?
Well, IPX203 is designed to address exactly the problem of immediate release carbidopa levodopa. So there are peaks and valleys. And IPX203, let’s start with the formulation. The concoction is actually very elegant and very simple, this he has two components. One is an immediate-release ingredient, so it is fast acting, absorbed quickly by the body, and provides immediate benefits. It’s a slow component you want to release, no peaks or troughs. It is designed to control symptoms and eliminate the side effects of dyskinesias and other side effects.
What is the efficacy that supports the efficacy of the drug?
We began development over five years ago, starting with Phase 1 pharmacokinetic studies to understand how drugs are absorbed in the body, how quickly and for how long. We then did a phase 2 trial. A Phase 2 study was conducted against Rytary, demonstrating that it is longer lasting than Rytary in terms of pharmacokinetic profile and superior to Rytary in terms of pharmacodynamics. We then performed a multiple-dose study to compare IPX203 to IR, again demonstrating significant superiority over IR CD-LD.
We then conducted a Phase 3 study, a pivotal study, which required approval. One was an efficacy study of approximately 500 patients, and the other was a safety study, in which patients were dosed open-label for nine months to determine efficacy and side effect profile. So those are the studies that supported the registry. In addition, three Phase 3 studies were conducted to understand food effects, dose proportionality, etc.
What is the key takeaway you want to convey to your audience today?
We believe that if IPX203 is approved, it will be the best oral CD-LD drug on the market. In terms of efficacy, a Phase 3 study showed that it was superior to immediate-release carbidopa levodopa when administered only 3 times daily or 5 times daily. Each dose lasted 1.6 hours longer than all doses of IR. Looking at the numbers, 2.2 hours vs. 3.7 hours. Effectiveness is measured on-the-fact with a 70% increase in efficacy. Good means you get efficacy without the side effects of dyskinesia. So, I think it’s a big benefit for patients to have access to less-frequently-used drugs that are more effective.
